Several methods for the oxidation of .alpha.-amino alcohols to .alpha.-amino aldehydes are known in the art: 1) dimethylsulfoxide (DMSO)/oxalyl chloride; 2) DMSO/trifluoroacetic anhydride; 3) DMSO/sulfur trioxide; and 4) DMSO/dicyclohexylcarbodiimide. These methods are variants of the well known Swern oxidation reaction.
Leanna et al., Tetrahedron Letters 33 (5) , 5029-32 (1992), disclose an oxidation process using 2,2,6,6-tetramethyl-1-piperidinyloxy free radical (TEMPO) for the preparation of Cbz-L-phenylalaninal from Cbz-L-phenylalaninol using ethyl acetate/toluene mixtures or dichloromethane as reaction solvent, 0.35M sodium hypochlorite solution, and the use of stoichiometric sodium bromide.
Complexation of vanadium(III) chloride with tetrahydrofuran (THF) is described in the literature (see Cotton et al., Inorg. Chem. (1985) 24, 913). Reduction of the complex with zinc to form Caulton's reagent: ##STR2## and coupling of Cbz-L-phenylalaninal to form (2S, 3R, 4R, 5S) -diol: ##STR3## is disclosed by Kempf et al., J. Org. Chem. 57, 5692 (1992) Kempf et al. describe a lengthy procedure for isolating and purifying the indicated diol diastereomer from the mixture of isomers produced in the reaction.
The following references disclose the preparation of noncyclic diaminediol compounds as HIV protease inhibitors: Dreyer et al., Biochemistry 32 (3), 937-47 (1993); Canadian Patent Application 2,026,832 (German Patent Application DE 4030350); European Patent Application No. WO 92/00948; European Patent Application Publication Number 402,646; U.S. Pat. No. 4,837,204; European Patent Application Publication Number 486,948; PCT International Publication Number WO 93/23,361.
The preparation of noncyclic diaminediol compounds as HIV protease inhibitors is also disclosed in Jadhav et al., U.S. Pat. No. 5,294,720.
Lam et al., PCT International Publication Number WO 93/07,128 discloses cyclic carbonyl compounds and derivatives thereof which are useful as human immunodeficiency virus (HIV) protease inhibitors for the treatment of HIV infection. The compounds disclosed in WO 93/07128 include cyclic HIV protease inhibitor compounds of the formula below where W may be --N(R.sup.22)C(=O)N(R.sup.23)--. ##STR4##
Copending commonly assigned U.S. patent application Ser. No. 08/197,630, filed Feb. 16, 1994 also discloses cyclic HIV protease inhibitors, including cyclic urea HIV protease inhibitors, of the formula below wherein W may be --N(R.sup.22)C(=O)N(R.sup.23)--. ##STR5##
As disclosed in Lam et al., PCT International Publication Number WO 93/07,128 and copending commonly assigned U.S. patent application Ser. No. 08/197,630, such cyclic sulfamide compounds, which may be made using the processes of the present invention, are non-peptidic, low molecular weight, orally bioavailable compounds useful as inhibitors of HIV protease and for the treatment of HIV infection. There is, therefore, a need for more efficient and cost-effective methods for the preparation of such cyclic urea HIV protease inhibitor compounds in high yields from readily available starting materials. The present invention provides improved processes for the synthesis of such cyclic urea HIV protease inhibitor compounds and processes for the synthesis of intermediates for the synthesis of such cyclic urea HIV protease inhibitor compounds.